Migration Induction Gene 7 (“Mig-7”). The present Applicant previously discovered an example of carcinoma-specific gene expression that is tightly regulated at transcription and translation, and is referred to as Migration Inducting Gene 7 (“Mig-7”, as referred to herein) (1;2). Mig-7 is a cysteine-rich protein localized to the cell membrane and cytoplasm whose mRNA and protein synthesis is atypical (1;2). Because of an unusual encoding region (DQ080207), and algorithms currently used to determine expression, Mig-7 or the ESTs to which it is homologous are not currently represented on any microarray even though its expression is restricted to carcinoma cells. Mig-7 expression is a result of receptor tyrosine kinase (RTK) activation in concert with ligation of .alpha.v.beta.5 integrin (.alpha.v.beta.5). Mig-7 antisense olignucleotide (ODN) but not inverted antisense ODN inhibits carcinoma cell scattering (1). Malignant tumors, blood from cancer patients and metastatic sites express Mig-7 regardless of tissue of origin. Notably, Mig-7 has not been detected in 25 different normal tissues (n=6 each tissue) or in blood from normal subjects (1;2).
Aggressive, invasive tumor cells can form vessel-like structures in 3D cultures. Laminin 5.gamma.2 promigratory fragments promote this vessel-like formation by aggressive melanoma cells in 3D cultures. In vivo, predominantly tumor rather than endothelial cells form vessels in the interior, more hypoxic region of tumors (3). Moreover, RTK-induced cancer cell migration, invasion and dissemination of aggressive carcinoma cells require .alpha.v.beta.5 signaling (4;5), the crosstalk that induces Mig-7, in vivo and in vitro (1). Fetal cytotrophoblasts are similar to cancer cells because they invade the maternal tissues during placenta development under RTK and .alpha.v.beta.5 signaling, evade immune system detection, endovascularly invade and are the only other cell type known to undergo vasculogenic mimicry (6). Surprisingly, Mig-7 cDNA is homologous to ESTs isolated from early invasive stage placenta as well as all cancer types studied while, in contrast, is not found in noninvasive term placenta or in other normal tissues (1;2). Moreover, Mig-7 is expressed by fetal cytotrophoblasts as well as carcinoma cells and plays a role in their common cell behavior of vessel-like structure formation and vascular remodeling. Moreover, as presently disclosed herein, adhesion assays to various components of the extracellular matrix suggests that a mechanism for Mig-7 in vessel formation by tumor cells is due to less adhesion to laminin.
There is a pronounced need in the art for compositions and methods to improved the specificity of cancer treatments to decease non-specific toxic side effects. There is a pronounced need for discovery and targeting of solid cancer-specific gene expression, particularly of broad-spectrum or pan-carcinoma expression, to provide for improved dosing and fewer side effects.